(1) Field of the Invention
The present invention generally relates to bioactive peptides. More specifically, the invention is directed to peptides that mimic melanocyte stimulating hormone by activating mammalian melanocortin receptors.
(2) Description of the Related Art
References Cited
Abreu M T, Fukata M, Arditi M. TLR signaling in the gut in health and disease. J. Immunol. 2005 Apr. 15; 174(8):4453-60.
Backhed F, Ley R E, Sonnenburg J L, Peterson D A, Gordon J I. Host-bacterial mutualism in the human intestine. Science. 2005 Mar. 25; 307(5717):1915-20.
Badman M K, Flier J S. The gut and energy balance: visceral allies in the obesity wars. Science. 2005 Mar. 25; 307(5717):1909-14.
Bardwell L. A walk-through of the yeast mating pheromone response pathway. Peptides. 2004 September; 25(9):1465-76. Review. Erratum in: Peptides. 2005 February; 26(2):337. Corrected and republished in: Peptides. 2005 February; 26(2):339-50.
Bhargava K, Templeton P, Spremulli L L. Expression and characterization of isoform 1 of human mitochondrial elongation factor G. Protein Expr Purif. 2004 October; 37(2):368-76.
Catania A, Delgado R, Airaghi L, Cutuli M, Garofalo L, Carlin A, Demitri M T, Lipton J M. α-MSH in systemic inflammation. Central and peripheral actions. Ann N Y Acad. Sci. 1999 Oct. 20; 885:183-7.
Catania A, Gatti S, Colombo G, Lipton J M. Targeting melanocortin receptors as a novel strategy to control inflammation. Pharmacol Rev. 2004 March; 56(1): 1-29.
Chai B X, Neubig R R, Millhauser G L, Thompson D A, Jackson P J, Barsh G S, Dickinson C J, Li J Y, Lai Y M, Gantz I. Inverse agonist activity of agouti and agouti-related protein. Peptides. 2003 April; 24(4):603-9.
Chandran P, Satthaporn S, Robins A, Eremin O. Inflammatory bowel disease: dysfunction of GALT and gut bacterial flora (I). Surgeon. 2003 April; 1(2):63-75.
Chhajlani V, Wikberg J E. Molecular cloning and expression of the human melanocyte stimulating hormone receptor cDNA (FEBS 11553). FEBS Lett. 1996 Jul. 22; 390(2):238.
Cone, R. D. (Ed) (2000). The Melanocortin Receptors. Humana Press Totowa, N.J., USA 551 pp.
Damcott C M, Sack P, Shuldiner A R. The genetics of obesity. Endocrinol Metab Clin North Am. 2003 December; 32(4):761-86.
Delgado R, Carlin A, Airaghi L, Demitri M T, Meda L, Galimberti D, Baron P, Lipton J M, Catania A. Melanocortin peptides inhibit production of proinflammatory cytokines and nitric oxide by activated microglia. J Leukoc Biol. 1998 June; 63(6):740-5.
Dumitriu I E, Baruah P, Manfredi A A, Bianchi M E, Rovere-Querini P. HMGB1: guiding immunity from within. Trends Immunol. 2005 July; 26(7):381-7.
Eberle, A. N. 2000 Propiomelanocortin and the Melanocortin Peptides. In The Melanocortin Receptors. R. D. Cone, editor. Humana Press, Totowa, N.J., USA. 3-67.
Eckburg P B, Bik E M, Bernstein C N, Purdom E, Dethlefsen L, Sargent M, Gill S R, Nelson K E, Relman D A. Diversity of the human intestinal microbial flora. Science. 2005 Jun. 10; 308(5728):1635-8.
Eckmann L. Innate immunity and mucosal bacterial interactions in the intestine. Curr Opin Gastroenterol. 2004 March; 20(2):82-8.
Farooqi I S, O'Rahilly S. Monogenic obesity in humans. Annu Rev Med. 2005; 56:443-58.
Federle M J, Bassler B L. Interspecies communication in bacteria. J Clin Invest. 2003 November; 112(9):1291-9.
Gallio M, Sturgill G, Rather P, Kylsten P. A conserved mechanism for extracellular signaling in eukaryotes and prokaryotes. Proc Natl Acad Sci USA. 2002 Sep. 17; 99(19):12208-13.
Gao J, Yu L, Zhang P, Jiang J, Chen J, Peng J, Wei Y, Zhao S. Cloning and characterization of human and mouse mitochondrial elongation factor G, GFM and Gfm, and mapping of GFM to human chromosome 3q25.1-q26.2. Genomics. 2001 May 15; 74(1):109-14.
Garside P, Millington O, Smith K M. The anatomy of mucosal immune responses. Ann NY Acad. Sci. 2004 December; 1029:9-15.
Gebbers J O, Laissue J A. Bacterial translocation in the normal human appendix parallels the development of the local immune system. Ann N Y Acad. Sci. 2004 December; 1029:337-43.
Gerst J E, Sole J, Hazum E, Salomon Y. Identification and characterization of melanotropin binding proteins from M2R melanoma cells by covalent photoaffinity labeling. Endocrinology. 1988 October; 123(4):1792-7.
Getz G S. Thematic review series: the immune system and atherogenesis. Immune function in atherogenesis. J Lipid Res. 2005 January; 46(I):1-10.
Greenberg E P. Bacterial communication and group behavior. J Clin Invest. 2003 November; 112(9): 1288-90.
Hammarsund M, Wilson W, Corcoran M, Merup M, Einhorn S, Grander D, Sangfelt O. Identification and characterization of two novel human mitochondrial elongation factor genes, hEFG2 and hEFG1, phylogenetically conserved through evolution. Hum Genet. 2001 November; 109(5):542-50.
Hansson G K. Inflammation, atherosclerosis, and coronary artery disease. N Engl J Med. 2005 Apr. 21; 352(16):1685-95.
Haynes R C Jr, Sutherland E W, Rall T W. The role of cyclic adenylic acid in hormone action. Recent Prog Horm Res. 1960; 16:121-38.
Henke J M, Bassler B L. Bacterial social engagements. Trends Cell Biol. 2004 November; 14(11):648-56.
Hoebe K, Janssen E, Beutler B. The interface between innate and adaptive immunity. Nat. Immunol. 2004:5(10):971-4.
Hruby, V. J. and Han G. 2000 The Molecular Pharmacology of A-Melanocyte Stimulating Hormone Structure-Activity Relationships for Melanotropins at Melanocortin Receptors. In The Melanocortin Receptors. R. D. Cone, editor. Humana Press, Totowa, N.J., USA. 239-261.
Janeway C A Jr, Medzhitov R. Innate immune recognition. Annu Rev Immunol. 2002; 20:197-216.
Kieber-Emmons et al., Curr. Opin. Biotechnol. 1997; 8:435-441.
Kita T, Inoue A, Nakanishi S, Numa S. Purification and characterization of the messenger RNA coding for bovine corticotropin/beta-lipotropin precursor. Eur J Biochem. 1979 Jan. 15; 93(2):213-20.
Korner J, Leibel R L. To eat or not to eat—how the gut talks to the brain. N Engl J Med. 2003 Sep. 4; 349(10):926-8.
Krude H, Biebermann H, Luck W, Horn R, Brabant G, Gruters A. Severe early-onset obesity, adrenal insufficiency and red hair pigmentation caused by POMC mutations in humans. Nat. Genet. 1998 June; 19(2):155-7.
Lefkowitz R J, Roth J, Pricer W, Pastan I. ACTH receptors in the adrenal: specific binding of ACTH-125I and its relation to adenyl cyclase. Proc Natl Acad Sci USA. 1970 March; 65(3):745-52.
Lenard J. Mammalian hormones in microbial cells. Trends Biochem Sci. 1992 April; 17(4): 147-50.
Lerner A B. The discovery of the melanotropins. A history of pituitary endocrinology. Ann N Y Acad. Sci. 1993 May 31; 680:1-12.
LeRoith D, Delahunty G, Wilson G L, Roberts C T Jr, Shemer J, Hart C, Lesniak M A, Shiloach J, Roth J. Evolutionary aspects of the endocrine and nervous systems. Recent Prog Horm Res. 1986; 42:549-87.
Li J, Kokkola R, Tabibzadeh S, Yang R, Ocliani M, Qiang X, Harris H E, Czura C J, Wang H, Ulloa L. Wang H, Warren H S, Moldawer L L, Fink M P, Andersson U, Tracey K J, Yang H. Structural basis for the proinflammatory cytokine activity of high mobility group box 1. Mol. Med. 2003 January-February; 9(1-2):37-45.
Li J, Wang H, Mason J M, Levine J, Yu M, Ulloa L, Czura C J, Tracey K J, Yang H. Recombinant HMGB1 with cytokine-stimulating activity. J Immunol Methods. 2004 June; 289(1-2):211-23.
Lipton J M, Macaluso A, Hiltz M E, Catania A. Central administration of the peptide α-MSH inhibits inflammation in the skin. Peptides. 1991 July-August; 12(4):795-8.
Lotze M T, Tracey K J. High-mobility group box 1 protein (HMGB1): nuclear weapon in the immune arsenal. Nat Rev Immunol. 2005 April; 5(4):331-42.
Maaser C, Kannengiesser K, Specht C, Luegering A, Brzoska T, Luger T A, Domschke W, Kucharzik T. Crucial role of the melanlocortin receptor MC1R in experimental colitis. Gut. 2006 Mar. 16; [Epub ahead of print] PMID: 16543288.
Macchia V, Bates R W, Pastan I. The purification and properties of a thyroid-stimulating factor isolated from Clostridium perfringens. J Biol Chem. 1967 Aug. 25; 242(16):3726-30.
Macdonald T T, Monteleone G. Immunity, inflammation, and allergy in the gut. Science. 2005 Mar. 25; 307(5717): 1920-5.
Mains R E, Eipper B A, Ling N. Common precursor to corticotropins and endorphins. Proc Natl Acad Sci USA. 1977 July; 74(7):3014-8.
Merritt, H. H. 1955 A textbook of neurology. Lea & Febiger. Philadelphia, U.S.A. 746 pp (see p. 47)
Mathesius U, Mulders S, Gao M, Teplitski M, Caetano-Anolles G, Rolfe B G, Bauer W D. Extensive and specific responses of a eukaryote to bacterial quorum-sensing signals. Proc Natl Acad Sci USA. 2003 Feb. 4; 100(3):1444-9.
McGeer P L, McGeer E G. Inflammation and the degenerative diseases of aging. Ann N Y Acad. Sci. 2004 December; 1035:104-16.
Mountjoy K G, Robbins L S, Mortrud M T, Cone R D. The cloning of a family of genes that encode the melanocortin receptors. Science. 1992 Aug. 28; 257(5074):1248-51.
Pasare C, Medzliitov R. Toll-like receptors: linking innate and adaptive immunity. Microbes Infect. 2004 December; 6(15): 1382-7.
Rendon-Mitchell B, Ochani M, Li J, Han J, Wang H, Yang H, Susarla S, Czura C, Mitchell R A, Chen G, Sama A E, Tracey K J, Wang H. IFN-gamma induces high mobility group box I protein release partly through a TNF-dependent mechanism. J. Immunol. 2003 Apr. 1; 170(7):3890-7.
Rielil R M, Toft D O. Analysis of the steroid receptor of Achlya ambisexualis. J Biol Chem. 1984 Dec. 25; 259(24):15324-30.
Ripka et al., Curr. Opin. Chem. Biol. 1998; 2:441-452.
Roberts J L, Herbert E. Characterization of a common precursor to corticotropin and beta-lipotropin: cell-free synthesis of the precursor and identification of corticotropin peptides in the molecule. Proc Natl Acad Sci USA. 1977 November; 74(11):4826-30.
Roth J, Leroith D, Collier E S, Watkinson A, Lesniak M A. The evolutionary origins of intercellular communication and the Maginot Lines of the mind. Ann N Y Acad. Sci. 1986; 463:1-11.
Saez J M, Evain D, Gallet D. Role of cyclic AMP and protein kinase on the steroidogenic action of ACTH, prostaglandin E1 and dibutyryl cyclic AMP in normal adrenal cells and adrenal tumor cells from humans. J Cyclic Nucleotide Res. 1978 August; 4(4):311-21.
Sanchez-Mas J, Hahmann C, Gerritsen I, Garcia-Borron J C, Jimenez-Cervantes C. Agonist-independent, high constitutive activity of the human melanocortin I receptor. Pigment Cell Res. 2004 August; 17(4):386-95.
Sanderson, Med. Res. Rev. 1999; 19:179-197.
Sartor R B. Review article: Role of the enteric microflora in the pathogenesis of intestinal inflammation and arthritis. Aliment Pharmacol Ther. 1997 December; 11 Suppl 3:17-22; discussion 22-3.
Sartor R B. Targeting enteric bacteria in treatment of inflammatory bowel diseases: why, how, and when. Curr Opin Gastroenterol. 2003 July; 19(4):358-65.
Schimmer B P, Ueda K, Sato G H. Site of action of adrenocorticotropic hormone (ACTH) in adrenal cell cultures. Biochem Biophys Res Commun. 1968 Sep. 6; 32(5):806-10.
Smith D W, Nagler-Anderson C. Preventing intolerance: the induction of nonresponsiveness to dietary and microbial antigens in the intestinal mucosa. J Immunol. 2005 Apr. 1; 174(7):3851-7.
Smythies L E, Sellers M, Clements R, Mosteller-Barnum M, Meng G, Benjamin W, Orenstein J M, Smith P. Human intestinal macrophages display profound inflammatory anergy despite avid phagocytic and bacteriocidal activity. J Clin Invest. 2005 January; 115(1):66-75.
Steinhoff U. Who controls the crowd? New findings and old questions about the intestinal microflora. Immunol Lett. 2005 Jun. 15; 99(1):12-6. Epub 2005 Jan. 21.
Taherzadeh S, Sharma S, Chhajlani V, Gantz I, Rajora N, Demitri M T, Kelly L, Zhao H. Ichiyama T, Catania A, Lipton J M. A-MSH and its receptors in regulation of tumor necrosis factor-α production by human monocyte/macrophages. Am J. Physiol. 1999 May; 276(5 Pt 2):R1289-94.
Taunton O D, Roth J, Pastan I. The first step in ACTH action: binding to tissue. J Clin Invest. 1967 June; 46(6): 1122-1129.
Thompson J D, Higgins D G, Gibson T J. CLUSTAL W: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position-specific gap penalties and weight matrix choice. Nucleic Acids Res. 1994 Nov. 11; 22(22):4673-80.
Schuiling G A. Deceive, and be deceived! J Psychosom Obstet. Gynaecol. 2004 June; 25(2): 170-4.
Urban S, Freeman M. Intramembrane proteolysis controls diverse signalling pathways throughout evolution. Curr Opin Genet Dev. 2002 October; 12(5):512-8.
Vaisse C, Clement K, Guy-Grand B, Froguel P. A frameshift mutation in human MC4R is associated with a dominant form of obesity. Nat. Genet. 1998 October; 20(2):113-4.
Wang H, Bloom O, Zhang M, Vishnubhakat J M, Ombrellino M, Che J, Frazier A, Yang H, Ivanova S, Borovikova L, Manogue K R, Faist E, Abraham E, Andersson J, Andersson U, Molina P E, Abumrad N N, Sama A, Tracey K J. HMG-1 as a late mediator of endotoxin lethality in mice. Science. 1999 Jul. 9; 285(5425):248-51.
Wang H, Yang H, Tracey K J. Extracellular role of HMGB1 in inflammation and sepsis. J Intern Med. 2004 March; 255(3):320-31.
Wichmann M W, Haisken J M, Ayala A, Chaudry I H. Melatonin administration following hemorrhagic shock decreases mortality from subsequent septic challenge. J Surg Res. 1996 October; 65(2):109-14.
Wilson C J, Finch C E, Cohen H J. Cytokines and cognition—the case for a head-to-toe inflammatory paradigm. J Am Geriatr Soc. 2002 December; 50(12):2041-56.
Yaffe K, Kanaya A, Lindquist K, Simonsick E M, Harris T, Shorr R I, Tylavsky F A, Newman A B. The metabolic syndrome, inflammation, and risk of cognitivedecline. JAMA. 2004 Nov. 10; 292(18):2237-42.
Yang H, Ochani M, Li J, Qiang X, Tanovic M, Harris H E, Susarla S M, Ulloa L, Wang H, DiRaimo R, Czura C J, Wang H, Roth J, Warren H S, Fink M P, Fenton M J, Andersson U, Tracey K J. Reversing established sepsis with antagonists of endogenous high-mobility group box 1. Proc Natl Acad Sci USA. 2004 Jan. 6; 101(1):296-301.
Yang H, Wang H, Czura C J, Tracey K J. The cytokine activity of HMGB1. J Leukoc Biol. 2005 July; 78(1):1-8. Epub 2005 Feb. 25.
Yeo G S, Farooqi I S, Aminian S, Halsall D J, Stanhope R G, O'Rahilly S. A frameshift mutation in MC4R associated with dominantly inherited human obesity. Nat. Genet. 1998 October; 20(2):111-2.
How does the innate immune system keep silent in the presence of the bacteria that reside normally in the host's intestinal tract (Janeway and Medzhitov, 2002; Steinhoff, 2005; Smith and Nagler-Anderson, 2005)? Among nature's densest collections of cells, these microbes are metabolizing continuously and proliferating (Eckburg et al., 2005; Backhed et al., 2005; Chandran et al., 2003). They are also very near to the body's largest lymphoid organ, the gut associated lymphoid tissue (GALT) (Chandran et al., 2003). The innate immune system, with sets of specific receptors, is continuously on the alert to recognize as well as respond promptly and vigorously to bacteria, alive or dead, as well as to molecular components of bacteria (Pasare and Bedzhitov, 2004; Hoebe et al., 2005; Macdonald and Monteleone, 2005; Abreu et al., 2005). Minute amounts of bacterial products typically activate the innate immune system's cellular and humoral responses designed to combat bacteria. Sometimes these responses may be so vigorous that they kill the host that is being defended.
We hypothesize that E. coli and other organisms in the flora of the intestine release substances that act via host cell receptors of hormones or hormone-like agents to maintain the normal quiescent state whereby the vast biomass of micro-organisms in the intestinal tract (existing at the highest density of cells in any known ecosystem) live in biological peace in the GI tract (dubbed by us pax intestinalis). By contrast, minute numbers of such organisms in blood or other body cavities typically activate rapidly multiple pathways of the innate immune system to generate a wide range of chemical and humoral responses (Janeway and Medzhitov, 2002; Steinhoff, 2005; Smith and Nagler-Anderson, 2005; Eckburg et al., 2005; Backhed et al., 2005; Chandran et al., 2003; Pasare and Bedzhitov, 2004; Hoebe et al., 2005; Macdonald and Monteleone, 2005; Abreu et al., 2005). Identification and characterization of these hypothesized substances are desirable to characterize bacterial mechanisms to escape mammalian immunity, and to develop treatments for diseases characterized by excessive reactions, such as inflammatory cytokine cascades. The present invention addresses that need.